Addition of MCP-1 and MIP-3β to the IL-8 appraisal in peritoneal fluid enhances the probability of identifying women with endometriosis.

Chemokines have been associated with endometriosis. Our study was aimed at evaluating the levels of six chemokines--CXCL8 (IL-8), CXCL12 (SDF-1), CCL2 (MCP-1), CCL5 (RANTES), CCL19 (MIP-3β), and CCL21 (6-Ckine)--in the peritoneal fluid (PF) of patients with and controls without endometriosis by multiplexed cytokine assay. In this retrospective case-control study conducted at the Charité University Hospital, patients (n = 36) and controls (n = 27) were enrolled. The patients were separated into groups according to stage of the disease: I-II (n = 21), III-IV (n = 1 5), and according to clinical findings: peritoneal endometriosis (PE; n = 7), deep-infiltrating endometriosis (DIE) affecting the retrocervical area (n = 13) or the bowel/rectovaginal site (n = 14). The subjects were also separated according to the cycle phase: follicular (n = 14) or luteal (n = 8) and the previous use (n = 25) or not (n = 38) of hormones. PF was collected from all subjects (n = 63) consecutively during laparoscopy. The concentration of chemokines in the PF was assessed using Luminex(®) x-MAP(®) technology. Sensitivity and specificity were calculated. A model of multiple logistic regressions estimated the odds of endometriosis for each combination of the chemokines detected. We observed significantly higher concentrations of IL-8 (p < 0.001), MCP-1 (p = 0.014), and MIP-3β (p = 0.022) in the PF of women with endometriosis than in the controls. A joint evaluation revealed that elevated levels of the three chemokines had a positive endometriosis prediction value of 89.1%. The combined assessment of MCP-1, MIP-3β, and IL-8 concentration in PF improved the likelihood of identifying patients with endometriosis. Future studies should investigate this panel in peripheral blood samples.

[1]  D. Socolov,et al.  The value of serological markers in the diagnosis and prognosis of endometriosis: a prospective case-control study. , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[2]  Stephen H Kennedy,et al.  Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. , 2011, Fertility and sterility.

[3]  E. Baracat,et al.  CD4+CD25highFoxp3+ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis , 2012, American journal of reproductive immunology.

[4]  P. Viganò,et al.  Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. , 2004, Human reproduction.

[5]  J. M. Wessels,et al.  Clinical markers of endometriosis: have we been too quick to judge? , 2014, Medical hypotheses.

[6]  J. Pinotti,et al.  The use of biochemical markers in the diagnosis of pelvic endometriosis. , 1997, Human reproduction.

[7]  Albert Zlotnik Chemokines and cancer , 2006, International journal of cancer.

[8]  Camila Scheffel,et al.  T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis. , 2011, Fertility and sterility.

[9]  C. Becker,et al.  Peripheral biomarkers of endometriosis: a systematic review. , 2010, Human reproduction update.

[10]  E. Sturlese,et al.  Interplay between Misplaced Müllerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis , 2013, Obstetrics and gynecology international.

[11]  K. Barnhart,et al.  Panel of markers can accurately predict endometriosis in a subset of patients. , 2008, Fertility and sterility.

[12]  K. Ballard,et al.  What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. , 2006, Fertility and sterility.

[13]  D. Aoki,et al.  Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis , 2014, Nature Communications.

[14]  B. De Moor,et al.  Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. , 2012, Human reproduction.

[15]  G. Halis,et al.  Combination of CCR1 mRNA, MCP1, and CA125 Measurements in Peripheral Blood as a Diagnostic Test for Endometriosis , 2008, Reproductive Sciences.

[16]  L. Alio,et al.  Evaluation of serum CA 125 levels in patients with pelvic pain related to endometriosis. , 2007, The International journal of biological markers.

[17]  Annalisa Capobianco,et al.  Endometriosis, a disease of the macrophage , 2013, Front. Immun..

[18]  P. Laudanski,et al.  Profiling of peritoneal fluid of women with endometriosis by chemokine protein array. , 2006, Advances in medical sciences.

[19]  C. Köhler,et al.  Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study. , 2008, Human reproduction.

[20]  E. Sturlese,et al.  Chronic Pelvic Pain in Endometriosis: An Overview , 2013, Journal of clinical medicine research.

[21]  N. Lunet,et al.  Are we employing the most effective CA 125 and CA 19-9 cut-off values to detect endometriosis? , 2005, European journal of obstetrics, gynecology, and reproductive biology.

[22]  L. Arendt-Nielsen,et al.  Correlation Between Altered Central Pain Processing and Concentration of Peritoneal Fluid Inflammatory Cytokines in Endometriosis Patients With Chronic Pelvic Pain , 2014, Regional anesthesia and pain medicine.

[23]  M. Simona,et al.  CD157-extracellular matrix proteins interactions enhance integrin-mediated signalling cascade in monocytes , 2013 .

[24]  S. Mechsner,et al.  Can chemokines be used as biomarkers for endometriosis? A systematic review. , 2014, Human reproduction.

[25]  B. De Moor,et al.  Biomarkers of endometriosis. , 2013, Fertility and sterility.

[26]  S. Mechsner,et al.  Reply: Biochemical markers for endometriosis: a long way to go. , 2014, Human reproduction.

[27]  I. Fraser,et al.  Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. , 2011, Journal of reproductive immunology.

[28]  C. Hernández-Guerrero,et al.  Quantitative and qualitative peritoneal immune profiles, T‐cell apoptosis and oxidative stress‐associated characteristics in women with minimal and mild endometriosis , 2011, BJOG : an international journal of obstetrics and gynaecology.

[29]  Salvatore Campo,et al.  Behavior of Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptor 1/Tumor Necrosis Factor Receptor 2 System in Mononuclear Cells Recovered From Peritoneal Fluid of Women With Endometriosis at Different Stages , 2015, Reproductive Sciences.

[30]  E. Baracat,et al.  Chemokines in the pathogenesis of endometriosis and infertility. , 2013, Journal of reproductive immunology.

[31]  C. Nicco,et al.  Role of the CXCL12-CXCR4 axis in the development of deep rectal endometriosis. , 2014, Journal of reproductive immunology.

[32]  Ann Richmond,et al.  Role of chemokines in tumor growth. , 2007, Cancer letters.

[33]  J. Kwak,et al.  Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes , 2011, Archives of Gynecology and Obstetrics.

[34]  R. Garry,et al.  Deeply infiltrating endometriosis affecting the rectum and lymph nodes. , 2006, Fertility and sterility.

[35]  E. Sturlese,et al.  Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. , 2011, Journal of reproductive immunology.

[36]  H. Martha,et al.  Endometriosis , 2015 .

[37]  R. Neme,et al.  Histological classification of endometriosis as a predictor of response to treatment , 2003, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[38]  Abbey C. Thomas,et al.  Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences. , 2012, Human reproduction.